The biological code used by proteins for recognition of nucleic acids is only now being investigated. This is an extremely important biological function since it relates to t-RNA interactions with ribosomes and synthetases, DNA interactions with polymerases and control proteins, DNA and RNA modification enzymes, the structure of chromatin and many other systems. Our efforts have been directed toward understanding this code in the lac operon of E. coli. Specifically, we have attempted to understand how lac repressor interacts with a small portion of this operon called the operator. When the repressor is bound at the operator site, the expression of this operon is blocked. Thus this interaction is important in relation to our understanding of gene regulation. As a result of our efforts during the past year, we now are quite confident about the nature of the DNA sites recognized by the lac repressor. Our results suggest that lac repressor interacts with both the major and minor grooves of lac operator DNA. Moreover this interaction is on one side of the DNA. Additionally these results reveal operator contact sites that stabilize the RO complex. Postulated strong contact sites on the operator DNA are the 5-methyl of thymine, the alpha-amino of guanine, the N7 of guanine and the central major groove functional groups. Weak contacts involving the 5-methyl of thymine have also been detected. Thus we feel that our results for the first time suggest a biological code used by proteins for recognizing DNA. We are presently extending these investigations to other systems as well.